Ibrutinib is A Bruton tyrosine kinase (BTK) inhibitor jointly developed by U.S. Johnson & Johnson and Pharmacyclics Inc. Since the compound has no standard Chinese translation, the applicant translated it as “Yilutini”. In February 2013, this drug received the qualification of “Breakthrough Therapy” by US Food and Drug Administration (FDA), and on Nov. 13, 2013, it was approved to appear on the markets. As a single treatment drug of mantle cell lymphoma, it is applicable to patients of mantle cell lymphoma previously treated by other means. Its trade name is Imbruvca. Ibrutinib is the first drug targeting BTK inhibitors appearing on the markets.
The chemical name of Ibrutinib is 1-[(3R)-3-[4-amino-3-(4-phenoxyphenyl) 1H-pyrazolo[3,4-D]pyrimidine-1-yl]-1-piperidinyl]-2-propen-1-one, having the structural formula as below:

The methods for preparing Ibrutinib were reported. US Patent No. US20080108636, No. US2008058528, No. US2009050897, No. US2010254905 and No. US2011039190 reported the synthesis of Ibrutinib and its analogs. In this method, 4-phenoxy-benzoic acid is used as starting material, after acylation, condensation, methoxylation, pyrazole cyclization, pyrimidine cyclization, N-alkylation, deprotection and acryloyl reaction, etc., functional groups are added, to finally prepare the target product. However, this routine needs a number of steps and a variety of unconventional materials and reagents, especially the trimethylsilyl diazomethane and polymer-supported triphenylphosphine have potential hazards and environmental pollution, thus, it is not suitable for industrial production.

The global patent No. WO2013003629 and Chinese Patent No. CN103121999 reported an improved method for preparing Ibrutinib. In the methods, 1H-pyrazolo[3,4-d]pyrimidine-4-amine is used as starting material, after iodination or bromination, the 3-iodo-1H-pyrazolo[3,4-d]pyrimidin-4-amine or 3-bromo-1H-pyrazolo[3,4-d]pyrimidin-4-amine is prepared. After Suzuki coupling reaction, Mitsunobu coupling reaction, deprotection and amidation reaction of the resulting halides, the target product is obtained. Compared with the original reactions, this synthetic method requires fewer steps but the overall yield is increased. However, since the preparation of parent ring 1H-pyrazolo[3,4-d]pyrimidin-4-amine is not involved and the preparation process needs halogenation, Suzuki coupling, Mitsunobu coupling reaction, the manufacturing costs and reaction conditions are not ideal.
